The Egyptian Journal of Radiology and Nuclear Medicine (2016) 47, 459–465

Egyptian Society of Radiology and Nuclear Medicine

The Egyptian Journal of Radiology andNuclearMedicine

www.elsevier.com/locate/ejrnmwww.sciencedirect.com

ORIGINAL ARTICLE

Value of integrated PET/CT in detection of hepatic

metastatic deposits

* Corresponding author.E-mail addresses: Dr.susanadil@hotmail.com (S.A. Ali), yasserib77@

gmail.com (Y.I. Abd Elkhalek).

Peer review under responsibility of The Egyptian Society of Radiology

and Nuclear Medicine.

http://dx.doi.org/10.1016/j.ejrnm.2016.03.0140378-603X � 2016 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier B.V.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Susan Adil Ali *, Yasser Ibrahim Abd Elkhalek

Radiodiagnosis Department, Ain Shams University, AL-Abbaseya, Cairo, Egypt

Received 18 December 2015; accepted 26 March 2016

Available online 9 April 2016

KEYWORDS

CT;

PET;

PET/CT;

Hepatic metastasis

Abstract Purpose: The goal of this study was to assess the value of combined PET/CT using 18F-

FDG in detection and characterization of hepatic metastatic lesions compared to isolated PET and

CT in various malignancies.

Patients and methods: The study included 82 patients divided into six groups of primary malignan-

cies to whom PET/CT scans were done. Detailed retrograde lesion based and patient based analyses

were performed for 441 detected hepatic lesions in 82 patients to detect metastasis on PET, CT and

PET/CT. A final diagnosis of metastasis was confirmed by biopsy or by further clinical and radio-

logic work-up.

Results: Regarding lesion based analysis, the PET/CT showed 98% sensitivity, 100% specificity,

100% PPV, 84% NPV and 98% accuracy compared with 98%, 98%, 99.7%, 84% and 98%, respec-

tively, for PET, and 95%, 81%, 98%, 63% and 94%, respectively, for CT. In patient-based anal-

ysis, PET/CT and PET showed 99% sensitivity, 100% specificity, 100% PPV, 90% NPV and 99%

accuracy compared with 100%, 56%, 95%, 100% and 95%, respectively for CT. The combined

PET/CT has significantly improved the low CT sensitivity as well as both CT and PET specificities.

Conclusion: PET/CT provides accurate detection of hepatic metastasis and their metabolic nature

which significantly affect further management.� 2016TheEgyptian Society ofRadiology andNuclearMedicine. Production andhosting byElsevier B.V.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-

nd/4.0/).

1. Introduction

The liver is the commonest site of hematogenous metastatic

spread. Hepatic metastatic focal lesions are 18–40 times morecommon than primary hepatic cancers (1). Metastases can

result from a wide variety of neoplasms, the most commonbeing from colorectal, breast, and primary lung cancers (2).Recent advances in different imaging techniques increased

the ability to detect and characterize hepatic focal lesions, withimprovements in diagnosis and monitoring of liver metastases(3). Unlike conventional imaging, (PET) positron emission

tomography combined with (CT) computed tomography(PET–CT) allows an evaluation of the physiological and bio-chemical processes underlying malignant disease. 18F-FDG

PET/CT shows high accuracy and sensitivity in the detectionof hepatic metastases derived from a wide range of primary

460 S.A. Ali, Y.I. Abd Elkhalek

malignant neoplasms (4). 18F-FDG PET has also been shownto be useful in assessing the chemotherapy treatment responseof hepatic metastases (5) especially in colorectal cancer (6). The

goal of our study was to assess the value of combined PET/CTusing 18F-FDG in detection and characterization of metastatichepatic focal lesions compared to isolated PET and CT in var-

ious malignancies.

2. Patients and methods

2.1. Patients

The study was performed in a retrospective way. The studypopulation included 82 cancer patients (48 male patients, 34female patients; mean age: 57.5; age range: 36–79) who under-

went whole body combined PET/CT scanning. The indicationsfor PET/CT examination were variable; 27 patients werereferred for initial disease staging and 55 patients for follow-up at variable disease stages. According to the type of primary

malignancies, the study population were divided into sixgroups. The type of primary malignancy has been histopatho-logically proven for all patients. The study excluded those who

had recent intervention (biopsy), radiotherapy or chemother-apy within 1 month from PET/CT scan.

2.2. PET/CT acquisition and processing

Combined PET/CT scan was performed using a hybrid PET/CT system (Ingenuity, TF PET/CT/Philips, the Netherlands).

The integrated CT system is a 64 multi-slice scanner. The acqui-sition of co-registered CT and PET images was performed inone session. Adequate patient preparation rules were strictlyfollowed. Patients were instructed to fast except for glucose-

free hydration for 4–6 h before injection of 18F-FDG. The scanwas performed 40–60 min after IV injection of 3.7 MBq/kg(maximum dose 370 MBq) equivalent to 0.1 mCi/kg (maxi-

mum dose = 10 mCi) of 18F-FDG. The patients were exam-ined in supine position. A whole body examination wasperformed starting from skull base to mid thighs.

A PET emission scan was performed over several bed posi-tions (5–7), each with an axial field of view of approximately15 cm per bed position with an in-plane spatial resolution of4 mm covering the same field of view as with CT. The acquisi-

tion time of emission data was 2 min per bed position in thetime range that was between 13 and 17 min.

A fully diagnostic CT scan was performed using the follow-

ing parameters: 350 mA, 120 kV, 0.5 s tube rotation time, slicethickness 5 mm, 8-mm table feed and 3 mm incremental recon-struction. IV contrast administration (80–120 mL) of a low-

osmolarity iodinated contrast agent and negative oral contrastagent (water) for bowel was used.

All PET, CT and PET/CT images were reconstructed and

viewed on Philips workstation, which provided multi-planarreformatted PET, CT and fused PET/CT images with linkedcursors as well as 3D maximum intensity projection (MIP)PET images in video mode.

2.3. Image analysis

A combined team, including one experienced nuclear medicine

physician and one experienced radiologist, interpreted the

PET, CT and fused PET/CT images. The PET images werereviewed by the nuclear medicine physician. The CT imageswere analyzed by the radiologist. Fused PET/CT images were

then analyzed separately by each of them, and each was blindto the other’s findings. They were aware of each patient’s his-tory and clinical data. The presence of hepatic metastases was

confirmed by biopsy or sequential various imaging modalitiesincluding CT, PET/CT, magnetic resonance imaging (MRI);performed during a follow-up of at least 6 months. In some

cases reviewing previous scans CT, MRI or PET/CT was alsodone to correlate recorded lesions.

2.3.1. Lesion based analysis

All focal lesions of abnormal FDG uptake were recordedand assessed quantitatively by measurement of the maximumstandardized uptake value (SUV max) for every lesion, and

malignant tumors tend to have SUV max values greaterthan 3.5 and exceeding background activity (by measuringSUV max value at surrounding liver parenchyma or medi-astinal blood pool in cases of diseased liver). Abnormalities

detected in the enhanced CT portion of the PET/CT studywere recorded, and then each lesion in the fused PET/CTimages was also evaluated. The metastatic deposits were

either non- enhancing, having marginal enhancement orintensely enhancing unlike cysts with fluid density or heman-giomas that show progressive contrast filling in dynamic

scans. Changes in lesion definition and localization providedby PET/CT were recorded. Our standard of reference washistopathologic examination or clinical and imaging follow-

up evaluation for at least 6 months together with confirma-tion of diagnosis by other modalities such as MRI used tocharacterize some of the lesions. A lesion was consideredtrue-positive (TP), if it exhibited progression at 6 months

of follow-up imaging, having other modality confirmingthe diagnosis of the lesions or if the histologic findings werepositive. A lesion was considered true-negative (TN), if the

lesion was unchanged at follow-up imaging and withoutclinical deterioration for at least 6 month or if the histologicfindings were negative and also if the patient performed

other examination such as MRI for evaluation of thislesions and confirmed its benign nature. A false negative(FN) lesion was considered when it was missed by the imag-ing modality and was positive histologically or confirmed to

be metastatic by other modality. On the other hand, a falsepositive (FP) lesion was detected on the imaging study, yet,proved to be negative histologically or by other modality.

2.3.2. Patient based analysis

A CT, PET or PET/CT study that showed at least 1 focallesion characterized as malignant and that was further con-

firmed to be malignant, was considered as true positive, andstudy of all lesions characterized as benign that showed no evi-dence of active cancer for at least 6 months was considered as

true-negative. Study of a patient with positive CT, PET orPET/CT who had no evidence of malignancy on biopsy orother imaging modalities, or a negative clinical follow-up of

at least 6 months, was classified as false-positive, and on theother hand a negative CT, PET or PET/CT study in a patientwho had further evidence of malignancy during the follow-up

was defined as false-negative.

Table 2 The CT, PET and PET/CT results, histopathology

and/or follow-up for assessment of 441 lesions in 77 patients.

No. of focal lesions PET/CT PET CT Histopathology

and/or follow-up

371 TP TP TP POSITIVE

20 TP TP FN POSITIVE

8 FN FN TP POSITIVE

8 TN TN FP NEGATIVE

1 TN FP TN NEGATIVE

33 TN TN TN NEGATIVE

true-positive TP; true-negative TN; false-positive FP; false-negative

FN.

Detection of hepatic metastatic deposits 461

3. Results

82 patients with histopathologically proven primary malig-nancy (Table 1), were evaluated for suspected hepatic metasta-

sis using combined PET/CT scans. Metastatic hepatic depositswere found in 77 patients, and 5 patients were free from hep-atic metastases.

3.1. Role of PET/CT in characterization of lesions: lesion-based

analysis

There were 441 focal lesions in the 77 patients evaluated(Table 2). Based on PET, CT and PET/CT, 371 lesions werecharacterized as active metastatic deposits and confirmedhistopathologically or on follow-up imaging (Figs. 1 and 2).

PET and PET/CT enabled the retrospective detection of 20lesions missed or not considered pathologic on CT. Malig-nancy was confirmed in 8 lesions by histologic specimens

obtained at surgery, by changes on follow-up imaging or con-firmed by MRI study, although they were negative on PET andPET/CT and interpreted as false negative. In 8 focal lesions the

CT study was defined as false positive for malignancy, whereasthe PET and PET/CT studies were true negative as these focallesions were non-viable (necrotic). None of these 8 focal lesionsdeveloped a recurrence on 6 months of follow-up. One lesion is

defined as false positive on PET study due to active pulmonarynodule based on the diaphragmatic pleura of right lung falselyinterpreted as a metastatic deposit at the dome of the liver;

however, it was confirmed to be pulmonary on both CT andPET/CT (Fig. 3). The remaining 33 lesions were benign lesions(simple cysts, hemangiomas and calcified granulomas) being

negative on PET/CT, PET and CT studies and interpreted astrue negative and were confirmed by other modalities.

According to the aforesaid data we calculated and com-

pared the performance indices of CT, PET and PET/CT forcharacterization of 441 lesions in 77 patients as regards sensi-tivity, specificity, positive predictive value (PPV), negative pre-dictive value (NPV) and accuracy (Table 3). PET/CT showed

sensitivity of 98%, specificity of 100%, PPV of 100%, NPVof 84% and accuracy of 98% compared with 98%, 98%,99.7%, 84% and 98%, respectively, for PET, compared with

95%, 81%, 98%, 63% and 94%, respectively, for CT data.

3.2. Evaluation of PET/CT diagnostic accuracy: patient-basedanalysis

82 patients were evaluated for suspected hepatic metastases(Table 4). CT, PET and PET/CT were true negative in 5 as

Table 1 Number of cases and their histopathologically

proven primary malignancy in the 82 patients.

No. of cases Primary malignancy

27 Cancer breast

23 Bronchogenic carcinoma

12 Cancer colon

8 Pancreatic carcinoma

7 Ovarian carcinoma

5 Malignant mesothelioma

they had no evidence of hepatic metastases. Hepatic metastaseswere the final diagnosis in 77 patients. 72 positive PET/CTstudies were true-positive with metastases proven by histologic

tissue sampling in 41 patients (about 57% of patients) and byother imaging during a follow-up of 6 months in 31 patients(about 43% of patients). Four negative PET/CT were true neg-ative showing necrotic non-viable metastases on histopatho-

logic sampling. These were also true negative on PET study,yet false positive on CT. On the other hand, one negativePET/CT study was false-negative with evidence of malignancy

on histopathological sampling. This patient had hepatic metas-tases from lung carcinoid tumor which is metabolically inerton PET and PET/CT as well its hepatic deposits; however, it

was true positive on CT (Fig. 4). PET and PET/CT showedsensitivity of 99%, specificity of 100%, PPV of 100%, NPVof 90% and accuracy of 99%. CT showed sensitivity of

100%, specificity of 56%, PPV of 95%, NPV of 100% andaccuracy of 95%.

4. Discussion

Contrast-enhanced multidetector-row CT is the primary imag-ing modality for the detection, localization, and characteriza-tion of focal liver lesions in many hospitals (7). Several

investigators have examined the incremental value of FDGPET as a supplement to CT and found that FDG PET offersinformation beyond that from CT alone and that this informa-

tion often affects patient care (8–10). FDG PET is highly sen-sitive for the detection of liver metastases (11–14), andcurrently FDG PET/CT is considered the most sensitive

non-invasive imaging method for the detection of hepaticmetastases, particularly from the gastrointestinal tract (15).A recent meta-analysis demonstrated the sensitivities of CT

and FDG PET for detecting hepatic metastases from CRCto be 83.6% and 94.1%, respectively (14). A study of PET–CT for the detection of recurrent or metastatic disease inpatients with a history of CRC and raised CEA found PET–

CT to be considerably better than multislice CT alone (16).Another study concluded that routine FDG-PET/CT assess-ment of patients with hepatic metastasis has a significant

impact on disease staging and selection of candidates suitablefor solitary liver metastasis resection and outcome (17).

In a patient-based analysis conducted by Abdel-Nabi et al.,

they have shown that it can be superior to CT for detectingliver metastasis. They reported sensitivity and specificity rates

Fig. 1 74 years old male with history of lung cancer and hepatic metastatic deposits received CTH and referred for follow-up. (a) CT

image shows two metastatic focal lesions at subsegments III and VII. (b) and (c) PET and PET/CT images show that both lesions show

increased 18F-FDG uptake with SUV max 9.1 and 7.6 respectively.

Fig. 2 30 years old male with recently diagnosed cancer colon and referred for initial staging. (a) CT images show multiple focal lesions

at subsegments IV and VII. (b) and (c) PET and PET/CT images show that these lesions are metabolically active with increased 18F-FDG

uptake showing SUV max 5–6.

462 S.A. Ali, Y.I. Abd Elkhalek

Fig. 3 41 years old female with history of endometrial carcinoma underwent TAH BSO, received CTH and RTH, and referred for

follow-up. (a) PET image shows a metabolically active lesion falsely interpreted to be at the dome of the liver. (b) CT, (c) axial PET/CT

and (d) coronal PET/CT images confirmed the pulmonary location of the nodule (active nodule at the base of right lung based on the

diaphragmatic pleura). Multiple other metabolically active pulmonary as well as subcarinal and left hilar LNs is also noted.

Table 3 Comparison of performance indices of CT, PET and PET/CT for characterization of 441 lesions in 77 patients (lesion-based

analysis).

No. of lesions TP TN FP FN Sensitivity (%) Specificity (%) PPV (%) NPV (%) Accuracy (%)

PET/CT 441 391 42 0 8 98 100 100 84 98

PET 441 391 41 1 8 98 98 99.7 84 98

CT 441 379 34 8 20 95 81 98 63 94

Table 4 Comparison of Performance Indices of PET/CT,

PET and CT based on patient-based analysis in 82 patients.

Indices PET/CT PET CT

TP 72 72 73

TN 9 9 5

FP 0 0 4

FN 1 1 0

Sensitivity (%) 99 99 100

Specificity (%) 100 100 56

PPV (%) 100 100 95

NPV (%) 90 90 100

Accuracy (%) 99 99 95

Detection of hepatic metastatic deposits 463

of 88% and 100%, respectively, with FDG-PET, comparedwith sensitivity and specificity rates of 38% and 97%, respec-

tively, with CT (18). In this study, according to the patientbased analysis, we found that PET/CT and PET showed

sensitivity of 99%, specificity of 100%, PPV of 100%, NPVof 90% and accuracy of 99% compared with 100%, 56%,

95%, 100% and 95%, respectively, for CT. So, combinedPET/CT improves the low CT specificity and increased itsaccuracy.

Another lesion-based analysis on the same study conductedby Abdel-Nabi et al., revealed on the basis of PET/CT a sen-sitivity, specificity, and accuracy of 100%, 89%, and 97%,

respectively, and a PPV and NPV of 97% and 100% and onthe basis of PET a sensitivity, specificity, and accuracy of96%, 50%, and 85%, respectively, and a PPV and NPV of85% and 82%, respectively (18). According to Orlacchio

et al., the PET study had 94.05% sensitivity, 91.60% specificityand 93.36% accuracy; the CT study had 91.07% sensitivity,95.42% specificity and 92.29% accuracy. The combined

PET/CT had 97.92% sensitivity, 97.71% specificity and97.86% accuracy (19). In a study by Zidan et al., in 2015a mul-

Fig. 4 59 years old male presented with recently diagnosed lung carcinoid tumor with multiple histopathologically proven hepatic

metastases. (a) CT image shows multiple variable sized focal lesions at both hepatic lobes. (b) and (c) PET and PET/CT images show not

any 18F-FDG uptake at the focal lesions, and were falsely interpreted as negative for malignancy.

464 S.A. Ali, Y.I. Abd Elkhalek

timodality assessment of hepatic focal lesions found that, on a

lesion based analysis, the sensitivity, specificity, PPV, NPV andaccuracy were 94%, 75%, 94%, 75%, and 90% for PET/CTcompared to 94%, 95%, 99%, 97% and 94% for MR, respec-

tively. Combined PET/CT-MR diffusion raises those parame-ters up to 100% (20). In the present study, according to lesion-based analysis, PET/CT showed sensitivity of 98%, specificity

of 100%, PPV of 100%, NPV of 84% and accuracy of 98%compared with 98%, 98%, 99.7%, 84% and 98%, respectively,for PET and sensitivity of 95%, specificity of 81%, PPV of

98%, NPV of 63% and accuracy of 94%, for CT. So, PET/CT was superior to PET and CT regarding the specificity(100%, 98%, and 81%, respectively) but superior only to CTregarding the sensitivity (98% for PET/CT compared to

95% for CT) and accuracy (98% for PET/CT compared to94% for CT).

5. Conclusion

PET/CT improved our ability to detect and characterize meta-static liver deposits, for proper staging which significantly

affect further management planning.

Conflict of interest

The authors declare that there are no conflict of interests.

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